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Big data, Genetics, Global Health, Infectious Disease, Research, Science

The benefit of mathematical models in medicine

The benefit of mathematical models in medicine

1024px-Free_range_chicken_flockTheoretical modeling sounds like it has, at best, a distant connection to the day-to-day concerns of medical professionals who care for or research the needs of patients. But when I spoke recently with Noah Rosenberg, PhD, a population geneticist at Stanford and editor of the scientific journal Theoretical Population Biology, he pointed out that modeling can offer distinct benefits to those in medical fields like epidemiology and genetics.

“We see a lot of occasions in public discussions of areas like the spread of epidemics, the demography of aging populations, and big data analysis in genomics where part of the backdrop arises from theoretical population biology work,” Rosenberg said. “We hope to spread the word that there is a place for the kinds of theoretical and mathematical insights that can contribute to those important topics.”

Rosenberg noted that papers in the journal often span the divide between mathematics and biology, but they have a few things in common. In an editorial he published last month in the journal, Rosenberg describes an ideal study for the journal – namely that first, “the mathematical work is motivated by a genuine problem in biology, and there’s a need for theory to resolve the problem,” he said. Secondly, the mathematical work is substantial enough that it uncovers new potential relationships or new explanations for a phenomenon, and lastly, that the advances contribute to our understanding of biology – though some of the best papers in the field can also have a big impact on the field of mathematics, too.

When I asked him to talk about what that would mean for studies that touch on health research, he pointed me to a couple of fascinating papers. One is a paper by Shai Carmi, PhD, and colleagues that explains a new way to look at shared DNA strands between people in order to understand their relatedness and the amount of overlap in their genomes. This has implications for how we think about “the way in which genes descend within families, including genes that may be related to a disease.” It’s one of the journal’s most downloaded papers, Rosenberg told me.

The second is a study by Maciej Boni, PhD, and colleagues that incorporates how decisions that poultry farmers in Southeast Asia make about market conditions might affect the spread of avian influenza in their flocks. When avian flu is identified in a region, poultry flocks are usually culled. It’s an interesting example of how human behavior can affect disease dynamics.

Rosenberg noted that the studies and models that are able to incorporate human behavioral patterns are among the most interesting that he sees. Nailing down how people’s decisions affect the course of an outbreak is notoriously difficult, but like the avian influenza paper demonstrates, mathematical models make it possible to explore the consequences of different assumptions about these decisions.

Rosenberg says that it’s even possible to make mathematical models of cultural practices (like deciding not to immunize your children) and how they spread among groups of people. One public laboratory this interaction is currently playing out in is the measles outbreak that got its start at Disneyland in December. The outbreak topped 100 cases nationwide, mostly among families that refuse to vaccinate their children. “It’s the intersection between human behavior and dynamics of disease,” he said. “Putting those together in a mathematical model to predict what might happen is the kind of work that appears in Theoretical Population Biology.”

Previously: Stanford physician Sanjay Basu on using data to prevent chronic disease in the developing world and Facebook app models how viruses spread through human interaction
Photo by Woodley Wonderworks

Global Health, Media, Patient Care, Pediatrics, Research, Technology, Videos

OPENPediatrics offers opportunity to help physicians, and sick children, worldwide

OPENPediatrics offers opportunity to help physicians, and sick children, worldwide

6948764580_97d353e8d4_zAs chief of critical care at Boston Children’s Hospital, Jeffrey Burns, MD, MPH, was asked to consult on the case of a young girl who fell ill while vacationing with her family in Guatemala. He had treated a similar case in the U.S. before, but he encountered unexpected technological hurdles.

That spurred Burns — working with many partners, including IBM — to create OPENPediatrics.org, a platform that allows physicians to share skills and resources to treat sick children. Burns described his hopes for the site in a 2014 article in Medtech Boston:

Our goal was to create something called a community of practice where instead of being broad and thin like a MOOC (Massive Open Online Classes), we would be narrow and much more deep, and the content would actually be peer reviewed by doctors and nurses who care for critically ill children, because those are essentially our primary users,” Burns says.

The site, which launched last year, offers forums for health-care workers worldwide to share experiences and a multimedia library with videos and animations — including some interactive features — on everything from nasopharyngeal suctioning to Faciltating Parent Presence During Invasive Procedures.

Burns and his team have been thinking how to leverage the platform to support research.

(A confession: I learned about OPENPediatrics through an article in Wesleyan magazine. Stanford’s Cardinal brethren on the East Coast, Wes, like Stanford fosters interdisciplinary projects and, I’m proud to say, is the alma mater of two of us in the medical school’s relatively small Office of Communication.)

Previously: Stanford undergrad works to redistribute unused medications and reduce health-care costs, Stanford Medicine X: From an “annual meeting to a global movement”  and Euan Ashley discusses harnessing big data to drive innovation for a healthier world
Photo by Intel Free Press

Global Health, Immunology, Research, Stanford News

With a Gates Foundation grant, Stanford launches major effort to expedite vaccine discovery

With a Gates Foundation grant, Stanford launches major effort to expedite vaccine discovery

Mark DavisThe vaccine field got a major boost today with the announcement that the Bill & Melinda Gates Foundation will invest $50 million in a new collaboration with Stanford’s School of Medicine to speed the development of vaccines for some of the world’s major scourges. The funds will support the new Stanford Human Systems Immunology Center, a multidisciplinary effort led by immunologist Mark Davis, PhD.

In recent decades, efforts to develop vaccines for major killers such as HIV and malaria have been stymied in part by the expense and time involved in conducting large-scale trials, which have often proved disappointing. Through the new initiative, scientists will use advanced immunological tools to better understand how vaccines provide protection and identify the most promising candidates to pursue in clinical trials.

What we need is a new generation of vaccines and new approaches to vaccination

“What we need is a new generation of vaccines and new approaches to vaccination,” said Davis, director of the Stanford Institute for Immunity, Transplantation and Infection. “This will require a better understanding of the human immune response and clearer predictions about vaccine efficacy for particular diseases.”

The 10-year initiative will involve multiple faculty from diverse fields, including medicine, engineering and computer science. It will capitalize on a range of technologies, some of which have been pioneered at Stanford, which can rapidly analyze individual cells and provide a detailed profile of the human immune response, with all of its various components.

“This grant will provide crucial support to Stanford’s world-class scientists as they collaborate with investigators around the globe to assess vaccines against some of the most formidable diseases of our time,” said Lloyd B. Minor, dean of Stanford’s medical school. “The Stanford Human Systems Immunology Center will help the most promising vaccine candidates to move quickly and efficiently from the lab to the front lines of treatment, impacting countless lives.”

Previously: Knight in lab: In days of yore, postdoc armed with quaint research tools found immunology’s Holy Grail
Photo of Mark Davis by Steve Fisch

Global Health, Health Policy, In the News, Infectious Disease

President Obama and Indian Prime Minister praise partnership that led to rotavirus vaccine

President Obama and Indian Prime Minister praise partnership that led to rotavirus vaccine

Barack_Obama_talks_with_Narendra_ModiDuring his three-day visit to India, President Barack Obama issued a joint statement with Indian Prime Minister Narendra Modi praising the “highly successful collaboration” that led to the availability of a newly developed Indian rotavirus vaccine, which is expected to save 80,000 children in India alone each year.

The vaccine was developed with support from the Indo-U.S. Vaccine Action Program, co-chaired since 2009 by Harry Greenberg, MD, senior associate dean for research at the Stanford School of Medicine. Greenberg was the lead inventor of the first-generation vaccine for rotavirus, a severe diarrheal disease that kills between 300,000 and 400,000 children each in the developing world.

“This is the VAP’s biggest accomplishment to date,” Greenberg told me from Taiwan, where he is attending a conference. “The program really helped support the development of a new safe and effective rotavirus vaccine from the start to finish. And it’s the first time ever that a new vaccine was developed in a less developed country by and for that country and became licensed.”

The vaccine initiative, funded by the U.S. Public Health Service and the Indian government, was created in 1987 to help advance the development of new vaccines of importance to India. The NIH manages research grants in the United States for the vaccine program.

“The VAP has been the most successful, continuous program we have with India,” Roger Glass, MD, PhD, director of the NIH’s Fogarty International Center, wrote in an email from India to top NIH officials. “It’s amazing to me that this little research project on rotavirus with Harry Greenberg and George Curlin (former deputy director of NIH’s Division of Microbiology and Infectious Diseases) has turned into a real product that is being launched and will be used.”

A low-cost version of the vaccine, known as Rotavac, is being manufactured in India and was launched into the marketplace on Jan. 23, Greenberg said. It was the result of an unusual team effort involving diverse multinational groups of investigators from 13 institutions seeking to create a vaccine that was not only safe and effective, but also affordable enough for use in India and other low-income countries, Greenberg said. The Indian government is negotiating to purchase the vaccine for public distribution. The vaccine also will compete in the private market against at least two other commercially available vaccines.

In the joint statement, the two world leaders pledged continued support for the vaccine program, and Greenberg, who recently stepped down from his chairmanship, made an argument for now focusing the attention of the vaccine partnership on respiratory syncytial virus (RSV), a potentially serious lung disease that is prevalent in children in India and in other regions as well.

“RSV is an incredibly important pediatric pathogen all over the world, and there is now potential for great progress,” Greenberg said. “I suggested to VAP that it think about RSV as a new target for research. It has a huge public impact and it may well be that there are great advances to be made in the near future. I think that idea resonated with the people. We will see.”

Previously: Life-saving dollar-a-dose rotavirus vaccine attains clinical success in advanced India trial and Trials, and tribulations, of a rotavirus vaccine
Photo courtesy of The White House

Global Health, Haiti, Research, Stanford News

Health care in Haiti: “At risk of regressing”

Health care in Haiti: "At risk of regressing"

streets of Haiti - smallAs an undergraduate at Duke University, Maxwell Kligerman stumbled into an amazing scientific opportunity. He spent the summer of 2009 collecting data on the availability of health-care facilities in Leogane, Haiti, a coastal city with a population of about 50,000 to support the work of Family Health Ministries, a non-profit founded by Duke reproductive endocrinologist David Walmer, MD.

With a guide, Kligerman walked every street in Leogane, tabulating the location and characteristics of even the most modest doctors’ offices.

His tally was important for local residents and some global health scholars, but certainly not anything with worldwide relevance.

We still need to keep Haiti on our radar. It’s been five years since the earthquake, but now is really the tipping point.

Then, on Jan. 12, 2010, the magnitude 7.0 Haitian earthquake struck, its epicenter just five miles from Leogane. Kligerman had unique, pre-earthquake data that could show the effects of the quake on local health-care opportunities. He could see what happened when the city experienced an influx of foreign aid and how the quake affected the trajectory of its development.

Taking advantage of his rare opportunity, Kligerman returned to Leogane in both 2011 and 2013, collecting information about the availability of health-care facilities.

Now, Kligerman is a third-year medical student at Stanford and recently published his findings in The American Journal of Tropical Medicine and Hygiene, in collaboration with Walmer and Stanford’s Michele Barry, MD, senior associate dean for global health, and Eran Bendavid, MD, assistant professor of medicine.

He has a critical message for those interested in global health: “We still need to keep Leogane and Haiti on our radar. It’s been five years since the earthquake, but now is really the tipping point.”

Before the earthquake, Leogane had 25 health-care facilities, ranging from a small doctors’ offices to large hospitals. Eleven of those buildings collapsed during the earthquake.

But soon, the international community swooped in, upping the number to 28. By 2013, Leogane had 34 healthcare facilities, many offering free care. Yet although the numbers look rosy, change is on the horizon.

Doctors without Borders, which operates the only full-service hospital, has announced plans to close the facility in 2015. That alone will dramatically reduce the availability of health care to Leogane residents, Kligerman said.

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Applied Biotechnology, Bioengineering, Global Health, Microbiology, Stanford News

Foldscope beta testers share the wonders of the microcosmos

Foldscope beta testers share the wonders of the microcosmos

Foldscopes-TanzaniaChristmas came early for citizen-scientists who received the first batch of Foldscope build-your-own paper microscope kits from Stanford’s Prakash Lab over the last several months. These beta testers have begun sharing a variety of fascinating images, videos, tips and ideas on the Foldscope Explore website.

From this site, you can watch Foldscope videos of fluid pulsing through the brain of a live ant or the suction mechanism of a fly foot. One citizen scientist analyzes the structural differences between his brown and gray hair follicles. Another provides a tutorial on FBI bird-feather forensics. (Germophobes might want to skip the close-ups of a face mite or the fungus that grows in half-eaten yogurt cartons.)

Half the fun of receiving a Foldscope kit is the unboxing and building process, which has been captured in YouTube videos by Foldscope fans Christopher and Eric.


lens-mounterEach kit includes parts for building two microscopes, multiple lenses, magnets that attach a Foldscope to a smartphone camera lens, slide mounts, and a battery-powered light module. This allows users to view magnified images with the naked eye or projected on a wall. Photos or videos of Foldscope images can easily be captured and shared via smartphones.

For those of you who haven’t received your Foldscopes yet, rest assured that those who signed up on the beta test site will receive them soon. It’s taking longer than anticipated to build and ship 50,000 microscopes. (The gadget on the right was custom-designed to insert the tiny spherical ball lenses into the magnetic smartphone-mounting platform.)

For Foldscope updates, sharing and inspirations, bookmark Foldscope Explore.

Previously: Stanford bioengineer develops a 50-cent paper microscopeStanford microscope inventor invited to first White House Maker Faire, The pied piper of cool science tools and Free DIY microscope kits to citizen scientists with inspiring project ideas
Photo of Foldscope co-inventor Jim Cybulski and Tanzanian children building foldscopes by Manu Prakash; photo of lens mounting gadget by Kris Newby

Global Health, Pediatrics, Public Safety, Research, Stanford News, Women's Health

Working to prevent sexual assaults in Kenya

Working to prevent sexual assaults in Kenya

Kenyan slumsThe little girl bounded up to us, wearing a filthy pink sweater, with a beaming smile on her face, and gave me a huge hug. Surprised at the reception, I hugged her back and swung her gently back and forth. She giggled and ran to hug my colleagues, then, hopping over an open sewer, darted into an alley that lead to her home. We followed as quickly as we could over the slippery mud, down one alleyway than another. Within a few minutes we reached her house, a 5’ by 10’ structure made of mud and wood, without windows, electricity, or locks. The girl, named Lianna*, lives here with her two year-old brother, who calls her “Mama”, as she is his primary caretaker. Their mother is a bartender and likely also a sex worker, and returns home only occasionally. The home is filthy, smells bad, and is without food or water. Yet this beautiful child, brimming with energy and intelligence, is proud to show it to us and to introduce us to her sibling.

Lianna is a resident of Korogocho, one of the poorest informal settlements (known to many as slums) in the Nairobi region of Kenya. Korogocho itself has about 52,000 residents, and it borders on other, larger informal settlements such as Dandora. Poverty and lack of sanitation are the norm in these communities, and crime is extremely high. Girls in these settlements may be especially vulnerable, with 18-25 percent of adolescent girls reporting being sexually assaulted each year, often by friends and relatives.

A multidisciplinary team at Stanford has been working in these communities on a sexual assault prevention project with two Kenyan non-governmental organizations (NGOs), Ujamaa and No Means No Worldwide (NMNW), for about two years. This past July, my colleague Mike Baiocchi, PhD, and I traveled to Kenya to meet the local NGO staff, become familiar with the communities they work in, and advance their research capacity.

Ujamaa, led by Jake Sinclair, MD, a pediatrician from John Muir Hospital, has been working in these and other settlements, including Kibera, Mathare, Huruma, Kariobangi, for more than 14 years, and has partnered with NMNW for several years. NMNW, led by Lee Paiva Sinclair, developed a curriculum to reduce sexual assault by teaching empowerment and self-defense, and works with Ujamaa to implement this curriculum in the slums. The Stanford team became involved in order to research the effectiveness of this intervention.

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Behavioral Science, Global Health, Neuroscience, Stanford News

Stanford Rhodes Scholar heading to Oxford to study ways "the brain can go awry"

Stanford Rhodes Scholar heading to Oxford to study ways "the brain can go awry"

10515175_10152524157302002_5878205180193467577_o-001Undergraduate Emily Witt is one of two Stanford students selected to receive the prestigious Rhodes Scholarship to study abroad at Oxford next year; an announcement was made late last month.

Witt is a human biology major with a concentration in neuropathology, and she’s minoring in psychology. Her research experience thus far spans neuroscience, psychology, autoimmune pathology, and health in the developing world; and she says she’s interested in studying “any way that the brain or the nervous system can go awry.”

Witt, who plans to attend medical school after her scholarship tenure, works in the lab of  neurologist Lawrence Steinman, MD, PhD, which seeks to understand the pathogenesis of autoimmune diseases, particularly multiple sclerosis. She’s using the lab to conduct research for her honors thesis, which focuses on the mechanisms of vitamin D in multiple sclerosis. She’s also involved with the Center for Interdisciplinary Brain Sciences Research and has participated in various studies related to autism and social cognition.

After hearing about this honor, I reached out to Witt with some questions about her work and her future plans:

How did you become interested in this field?

I’m interested in MS for two reasons. On a personal level, I have seen the devastating impact of the disease first-hand as my uncle has the progressive form of MS. Watching his condition worsen, and seeing the impact it has had on his life and the life of my aunt and cousins, inspired me to research this horrible disorder.

On an intellectual level, I’m fascinated by the interaction between the immune system and the brain. I believe it’s an incredibly important area of research as the immune system is a contributing factor to numerous neurological diseases, from multiple sclerosis and autism to depression.

What makes Oxford a particularly appealing place for you to study? Who or what do you hope to work with there?

I’m interested in working with two neuroscientists who are experimental psychologists; they’re actually bridging the gap between experimental psychology and neuroscience, which are the two degrees I’m hoping to pursue while at Oxford. One is Elaine Fox, who researches cognitive biases, and the other is Catherine Harmer, [who studies the] pharmacological aspects of depression and how they affect cognitive biases, particularly with respect to depression and anxiety.

Are you interested in contextual understandings of disease or degeneration – its social roots? How does interdisciplinary work fit into your imagining of what you’re doing and would like to do?

That’s what my primary motivation going forward is: kind of connecting what I see in everyday life and how neurological [diseases] manifest and what I understand about them biologically. So what I’m really interested in is combining a fundamental understanding of psychology with clinical applications of neuroscience… Because I do think that… there’s still a wide gap between studying the brain on a molecular and cellular level, and studying it on a behavioral level.

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Global Health, Infectious Disease, Microbiology, Public Health, Videos

'Tis the season for norovirus

'Tis the season for norovirus

The week before Thanksgiving, some kind of stomach bug, which I suspect was norovirus, spread like wildfire among my daughter’s daycare. Several of her classmates became sick and like dominos so did the parents, including us.

So I was more than sympathetic when I came across this video by John Green (of the vlogbrothers fame and author of “The Fault in Our Stars”) about his family’s Thanksgiving troubles with a norovirus infection that seems to have left no GI system untouched in their household.

Winter, from about November to April, is prime norovirus season. The treacherous illness, which as Green says “has amazing superpowers,” spreads when you come into contact with feces or vomit of an infected person. It can take less than a pinhead of virus particles to make this happen. Unlike other viruses, it can live on surfaces for surprising long periods, which is how a reusable grocery bag caused an outbreak among a girls soccer team in 2012. Plus, an infected person can continue to shed the virus for about three or four days after recovering. It’s possible to disinfect after an infection, but it’s a pretty intense job.

Given these characteristics it’s not surprising that this tiny virus (even by virus standards) causes about 20 million illnesses each year. Although for most people it’s a mild illness, for the very young,  old or those with compromised immune systems—it can be severe. About 56,000-71,000 people are hospitalized and 570-800 die from norovirus infections.

The situation is worse in developing countries, where, as Green points out, rehydration therapy is harder to come by for the most vulnerable. About 200,000 deaths are caused by norovirus infections in poor parts of the world.

In his typical funny and thoughtful style, Green talks about what lack of simple—and cheap—rehydration therapy means for many on our planet. It’s one more thing that it’s easy to take for granted, and one more thing to be thankful for.

Previously: Stanford pediatrician and others urge people to shun raw milk and products and Science weighs in on food safety and the three-second rule

Global Health, Infectious Disease, Stanford News

Back home from Liberia, Stanford physician continues to help in fight against Ebola

Back home from Liberia, Stanford physician continues to help in fight against Ebola

Colin Bucks - 560

Earlier this fall, we shared the story of Stanford physician Colin Bucks, MD, who, as a volunteer with the International Medical Corp, treated some 130 patients with Ebola in Liberia. Bucks is home now (he emerged from a 21-day home isolation on Nov. 14) but is still helping from afar. As reported by Inside Stanford Medicine:

Since his return to California, Bucks has been much in demand as a member of a small cadre of clinicians who have had direct experience with Ebola. He’s been working with health professionals at universities and nonprofits around the world who are doing research on new approaches to combating the disease, tracking trends in the epidemic and developing new designs for protective gear, which are cumbersome and stifling, he said.

“The heat stress is massive,” he said. “Your vision is limited. So anything we can do to improve PPE [personal protective equipment] will help improve patient care.”

During his quarantine, he said he did not have a moment of boredom; he was on the phone for 15 hours at a stretch consulting with health experts across the country on Ebola preparedness and on the needs in West Africa…

Previously: Stanford physician shares his story of treating Ebola patients in Liberia

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